Thrombin is known to have a variety of activities in different cell types and thrombin receptors are known to be present in such cell types as human platelets, vascular smooth muscle cells, endothelial cells, and fibroblasts. Thrombin receptor antagonists may be useful in the treatment of thrombotic, inflammatory, atherosclerotic and fibroproliferative disorders, as well as other disorders in which thrombin and its receptor play a pathological role. See, for example, U.S. Pat. No. 6,063,847, the disclosure of which is incorporated by reference.
One thrombin receptor antagonist is compound A, and salts thereof:

This compound is an orally bioavailable thrombin receptor antagonist derived from himbacine. Compound A may be synthesized from Compound 2A:
wherein R2 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl and R3, R4 and R5 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, arylalkyl, and heteroaryl; or, R4 and R5, together with the carbon atom to which they are attached, form a 5- to 7-membered ring having from 0-3 heteroatoms as ring members.
Processes for the synthesis of similar himbacine analog thrombin receptor antagonists are disclosed in U.S. Pat. No. 6,063,847, and U.S. application Ser. No. 10/412,982, and the synthesis of the bisulfate salt of a particular himbacine analog is disclosed in U.S. application Ser. No. 10/755,066, the disclosures of which are incorporated by reference herein.